Haemodynamic Assessment by Transvalvular Impedance Recording

Recording

M.G. B ONGIORNI

, E. S OLDATI

, G. A RENA

, G. G IANNOLA

, C. B ARTOLI

, A. B ARBETTA

, F. D I G REGORIO

Full autoregulation of a pacing device is an important prospect in the advancement of cardiac stimulation, which is expected to integrate in a glob- al controlling system several automatic functions such as mode switching, rate-responsive pacing, adaptation of sensitivity and pulse energy, AV delay tuning, and more. Since the final aim of cardiac pacing is ensuring a blood supply that properly matches the patient’s functional conditions, haemody- namic sensors could be proposed as the best candidates for supervision of an implantable pacemaker. However, currently available haemodynamic sen- sors, such as peak endocardial acceleration (PEA) or unipolar ventricular impedance, have been designed to monitor processes and parameters corre- lated with the ventricular contraction strength [1–4], whereas adequate haemodynamic control of cardiac function would better be achieved through assessment of the ejected blood volume [5, 6].

Volume Information from Impedance Data

So far, no one has attempted to include a flowmeter in the design of a perma- nent stimulator, since such a sensor would be too complex and unreliable in the long run. On the other hand, suitable information on the stroke volume (SV) trend can be derived by measuring the electric impedance of the ventri- cle, which is proportional to the distance between the sampling points and inversely related to the cross-sectional area of the conducting medium [7].

Any change in ventricular blood volume should entail a corresponding change in intraventricular impedance. The ideal tool to correlate impedance and volume changes is a multipolar catheter, as currently used in acute

1

CardioThoracic Department, University of Pisa;

Medico Clinical Research, Rubano

(Padua), Italy

haemodynamic studies [8, 9]. However, impedance fluctuations induced by ventricular mechanical activity can be detected even with conventional pac- ing leads, in either unipolar or bipolar modality. Unipolar impedance, mea- sured between the tip ventricular electrode and the pacemaker case, is thought to be modulated by structural modifications in the electrode’s microenvironment. The main information extracted from the unipolar impedance signal is a score of the fluctuation steepness, which can be affect- ed by the contraction strength [3, 10]. Bipolar intraventricular impedance, recorded between the tip and the ring ventricular electrode, has been sug- gested to be mainly dependent on the ventricular volume. In this case as well, the system should be sensitive just to local events in the ventricular apex, which is taken as a representative sample of the whole ventricle. The absolute values of minimum and maximum bipolar impedance in a cardiac cycle are sensitive to preload and contractility modifications, and the report- ed changes are consistent with the hypothesis of an inverse relationship between ventricular impedance and volume [5, 6, 11].

Indeed, impedance measurements are known to be affected by additional factors, including electrode position and movement. Special care in data management has been suggested to remove non-specific effects and max- imise the impedance sensitivity to volume changes [6]. In addition, further advantages were produced by the development of an alternative method for cardiac impedance recording, i.e. the assessment of transvalvular impedance (TVI). TVI is measured between an atrial and a ventricular electrode, thus increasing the dipole length with respect to the intraventricular impedance while keeping both the poles inside the heart [12–14]. This virtually avoids the artefacts produced by thorax movement, which affect the unipolar ven- tricular impedance, allowing impedance recording without high-pass filter- ing. In the presence of a bipolar ventricular lead, TVI can be measured with either the tip or the ring ventricular electrode [15]. In the latter case, there is no close contact with the ventricular wall, and therefore cyclic impedance changes should better reflect pure volume modifications associated with the pump function.

Transvalvular Impedance as a Haemodynamic Indicator

The TVI waveform generally features high stability and signal-to-noise ratio,

even with DC coupling. The absolute minimum and maximum TVI are

recorded, respectively, in telediastole and telesystole, and are assumed to be

inversely related to the maximum and minimum ventricular volume. Studies

conducted with external devices connected to the pacing leads during pace-

maker implantation or replacement procedures confirmed that end-diastolic

TVI (edTVI) depends on the preload, while end-systolic TVI (esTVI) is sen- sitive to cardiac contractility. In these experiments, preload modifications were produced by cardiac rate changes, while positive inotropic and chronotropic effects were induced by the administration of a beta-adrener- gic drug. All the patients were lying supine and could not move during the test [15–17].

To overcome these limitations, we recorded TVI in patients undergoing the extraction of infected pacing leads. In such cases, it is normal practice to expose the lead connectors before the extraction procedure for pocket drain- ing. This made possible connecting an external device with chronically implanted leads in patients free to move, in order to study the TVI response to postural changes and physiological autonomic stimulation during an ergometric stress test.

The transition from lying supine to standing upright is known to entail a reduction in ventricular filling due to the opposing action of gravity, with consequent blood accumulation in the leg veins and corresponding SV decrease imposed by the intrinsic regulation of the heart. This effect is phys- iologically counteracted by a positive chronotropic reaction, aimed at main- taining an adequate cardiac output. In these circumstances, we observed a reversible reduction in the peak-to-peak excursion of the TVI signal, result- ing from an increase in edTVI (Fig. 1). Data were processed considering the peak-to-peak TVI amplitude as a SV indicator [5, 11]. The relationship between the two parameters was assumed to be approximately linear in the physiological range. Any change in edTVI or esTVI with respect to their baseline values was expressed as a percentage of the peak-to-peak TVI amplitude at rest and represented an equal and opposite volume change, expressed as a percentage of the baseline SV. According to this model, the TVI modifications induced by standing up indicated a 20% decrease in SV with respect to the supine position, ascribed entirely to a preload reduction (Fig. 2).

A physical stress test was performed on the ergometric bicycle, increasing the power by 20 W every 3 min. At the start of exercise, TVI measurements indicated an increase in SV, resulting from both an increase in end-diastolic volume (EDV) and a decrease in end-systolic volume (ESV). With increasing workload EDV was constant, whereas ESV kept on slowly decreasing. When the exercise was stopped, EDV and SV dropped quickly, whereas ESV remained reduced in the early recovery stage (Fig. 3). The results suggest that SV adaptation was achieved by the contribution of both intrinsic and extrinsic cardiac regulation. Skeletal muscle activity readily increased the venous return and the preload, which rapidly dropped at the end of exercise.

On the other hand, the autonomic nervous system induced a progressive

increase in both sinus rate and myocardial contractility. The enhanced con-

Fig. 2. Modifications in ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and stroke volume (SV) induced by the transition from supine to upright stand- ing, as inferred from TVI data. The asterisks indicate statistically significant variations.

Volume changes are scaled in arbitrary units, corresponding to 1/100 of the reference SV, and are derived by expressing the changes in edTVI, esTVI, and peak-to-peak TVI as a percentage of the peak-to-peak TVI excursion recorded in the supine position. The variations in EDV and ESV are equal and opposite to the corresponding normalised TVI changes: an impedance increase represents an equivalent volume decrease, while an impedance decrease represents a volume increase

Fig. 1a, b. From top to bottom: transvalvular impedance (TVI), ventricular and atrial electrograms, surface ECG. An external recorder was connect- ed w ith exposed chronic pacing leads, prior to lead extrac- tion, while VDD pac- ing was performed by a new contralateral implant. This explains the double signal shown in the ventricular electrogram: the first deflection is the artefact produced by the spike delivered by the contralateral lead; the second is the R wave detected after a conduction delay. a Supine position. The sinus rate was 90 ± 4 bpm. End-diastolic TVI (edTVI), end-systolic (esTVI) and peak-to-peak TVI excursion averaged, respectively, 420 ± 3, 483 ± 1,and 63 ± 3 Ω.b Standing upright.The sinus rate increased to 116 ± 3 bpm.EdTVI, esTVI and peak-peak TVI were 432 ± 4, 483 ± 2, and 51 ± 5 Ω, respectively. The changes in edTVI and peak-to-peak TVI were highly significant (P < 10

, Student’s t-test)

a b

tractility entailed a reduction in the residual ESV, which lasted longer than sinus tachycardia when the exercise was stopped. This could be due to the different physiological regulation of ventricular myocytes and sinus node fibres, since the former are mainly sensitive to the sympathetic influence, while the latter are markedly dependent on both sympathetic and parasym- pathetic control.

In the case of either preload or contractility changes, the information derived from TVI was in agreement with the physiological expectation, sug- gesting the general reliability of the proposed haemodynamic model and supporting the hypothesised correspondence between TVI and ventricular volume. The TVI sensor can provide indications as to the inotropic state of the heart, which can be useful in patient follow-up and in the regulation of rate-responsive pacing. Indeed, the TVI-indicated rate closely reproduced the sinus rate trend during adrenergic challenge in patients with good chronotropic competence [17].

Fig. 3a, b. Stress test on the ergometric bicycle; the arrows indicate the end of the exercise. Changes in SV, EDV and ESV are derived from TVI data. a Relative variation in sinus rate and SV. b Relative changes in EDV and ESV.

The modifications in min- imum and maximum TVI values in each cardiac cycle were converted into corresponding volume changes, as described for Fig. 2

a

b

Haemodynamic Surveillance of Pacing and Sensing

An essential piece of information to be expected from a haemodynamic sen- sor concerns the occurrence of systolic ejection, whatever the SV or the myocardial contractility. Thanks to the excellent signal-to-noise discrimina- tion, TVI proved reliable in the check for correct association of electrical and mechanical events at every heartbeat, in the case of either evoked or intrinsic activity. After ventricular pacing, a significant TVI increase detect- ed in the systolic window allows confirmation of capture [12, 13, 18]. After ventricular sensing, a TVI response is expected as well: if it does not occur, the reality of the recorded electric event should be questioned. The applica- tion of the TVI sensor in ventricular pacing and sensing validation has been successfully tested with an external pacemaker, which reacted to capture loss by increasing the pulse energy and to TVI-indicated electric interference with the sensing function by switching over to a ventricular-triggered pacing mode [18]. The system proved equally sensitive to evoked or intrinsic ven- tricular activation, thus ensuring the prompt detection of possible fusion beats (Fig. 4).

Fig. 4. Surface ECG (upper tracing)

and corresponding TVI waveform

(middle) and event markers (low-

er tracing), recorded by an exter-

nal pacemaker. Threshold analysis

in VVI pacing (downward mark-

ers). Ventricular capture entails

clear-cut TVI responses, until an

ineffective spike is delivered. In

this case, the TVI signal remains at

the baseline, allowing capture loss

recognition (upward alarm mark-

er) and automatic pulse energy in-

crease. The following event is a fu-

sion beat, producing a TVI fluctu-

ation promptly detected by the

pacemaker (no further alarm

markers are released). Thereafter,

effective overdrive pacing is re-

gained. Note the different mor-

phology of the TVI signal in case

of VVI pacing (positive deflection)

or intrinsic conduction (biphasic waveform, starting with a smaller negative deflection as-

sociated with the P wave on the surface ECG and indicating active ventricular filling). In

this test, several episodes of capture loss were induced. After ineffective stimulation, the

TVI noise never exceeded 20% of the reference signal. As a result, the capture validation

algorithm based upon the TVI sensor showed 100% sensitivity and specificity

Conclusions

Effective haemodynamic sensing would open the way to the autoregulation of a number of pacemaker functions, which could thus be integrated into a single control system. The TVI sensor can be proposed to play this crucial role, allowing the assessment of systolic and diastolic modifications in ven- tricular volume by means of conventional pacing leads.

References

1. Pichlmaier AM, Braile D, Ebner E et al (1992) Autonomic nervous system control- led closed loop cardiac pacing. Pacing Clin Electrophysiol 15:1787–1791

2. Rickards AF, Bombardini T, Corbucci G et al (1996) An implantable intracardiac accelerometer for monitoring myocardial contractility. Pacing Clin Electrophysiol 19:2066–2071

3. Osswald S, Cron T, Gradel C et al (2000) Closed-loop stimulation using intracardiac impedance as a sensor principle: correlation of right ventricular dP/dt max and intracardiac impedance during dobutamine stress test. Pacing Clin Electrophysiol 23:1502–1508

4. Plicchi G, Marcelli E, Parlapiano M et al (2002) PEA I and PEA II based implantable haemodynamic monitor: pre clinical studies in sheep. Europace 4:49–54

5. Chirife R, Tentori MC, Mazzetti H, Dasso D (2001) Hemodynamic sensors: are they all the same? In: Raviele A (ed) Cardiac arrhythmias 2001. Springer, Milan, pp 566–575

6. Chirife R (2003) Hemodynamic assessment with implantable pacemakers. How feasible and reliable is it? In: Raviele A (ed) Cardiac arrhythmias 2003. Springer, Milan, pp 705–712

7. Arthur W, Kaye GC (2001) Clinical use of intracardiac impedance: current applica- tions and future perspectives. Pacing Clin Electrophysiol 24[Pt I]:500–506

8. Applegate RJ, Cheng CP, Little WC (1990) Simultaneous conductance catheter and dimension assessment of left ventricular volume in the intact animal. Circulation 81:638–648

9. Kass D, Chen-Huan C, Curry C et al (1999) Improved left ventricular mechanics from acute VDD pacing in patient with dilatated cardiomyopathy and ventricular conduction delay. Circulation 99:1567–1573

10. Griesbach L, Gestrich B, Wojciechowski D et al (2003) Clinical performance of automatic closed-loop stimulation systems. Pacing Clin Electrophysiol 26[Pt I]:1432–1437

11. Chirife R, Ortega DF, Salazar A (1993) Feasibility of measuring relative right ventri- cular volumes and ejection fraction with implantable rhythm control devices.

Pacing Clin Electrophysiol 16:1673–1683

12. Di Gregorio F, Morra A, Finesso M, Bongiorni MG (1996) Transvalvular impedance (TVI) recording under electrical and pharmacological cardiac stimulation. Pacing Clin Electrophysiol 19[Pt II]:1689–1693

13. Bongiorni MG, Soldati E, Arena G et al (1997) Trans valvular impedance as a

marker of cardiac activity. In: Vardas PE (ed) Europace ’97. Monduzzi, Bologna, pp

525–528

14. Morra A, Panarotto D, Santini P, Di Gregorio F (1997) Transvalvular impedance (TVI) sensing: a new way toward the hemodynamic control of cardiac pacing. In:

Vardas PE (ed) Europace ’97. Monduzzi , Bologna, pp 529–533

15. Gasparini M, Curnis A, Mantica M et al (2001) Hemodynamic sensors: what clini- cal value do they have in heart failure? In: Raviele A (ed) Cardiac arrhythmias 2001. Springer, Milan, pp 576–585

16. Di Gregorio F, Curnis A, Pettini A et al (2002) Trans-valvular impedance (TVI) in the hemodynamic regulation of cardiac pacing. In: Mitro P, Pella D, Rybár R, Valoc

ik G (eds) Cardiovascular diseases 2002. Monduzzi, Bologna, pp 53–57 17. Gasparini G, Curnis A, Gulizia M et al (2003) Can hemodynamic sensors ensure

physiological rate control? In: Raviele A (ed) Cardiac arrhythmias 2003. Springer, Milan, pp 725–731

18. Bongiorni MG, Soldati E, Arena G et al (2003) Transvalvular impedance: does it allow automatic capture detection? In: Raviele A (ed) Cardiac arrhythmias 2003.

Springer, Milan, pp 733–739